(-)-15-methylene-eburnamonine | 1294506-25-4

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - Eburnan型生物碱
• 英文名称: (-)-15-methylene-eburnamonine
• 英文别名: 15-methylene-eburnamonine；α-methylene-(-)-eburnamonine；(15S,19S)-15-ethyl-16-methylidene-1,11-diazapentacyclo[9.6.2.02,7.08,18.015,19]nonadeca-2,4,6,8(18)-tetraen-17-one
• CAS: 1294506-25-4
• 化学式: C₂₀H₂₂N₂O
• 分子量: 306.407
• InChiKey: BYKPJQXMXVPGMZ-QUCCMNQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  25.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (-)-15-methylene-eburnamonine 在 palladium on activated charcoal 、 氢气 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 72.0h， 以85%的产率得到(15S,16R,19S)-15-ethyl-16-methyl-1,11-diazapentacyclo[9.6.2.02,7.08,18.015,19]nonadeca-2,4,6,8(18)-tetraen-17-one
  参考文献：
  名称：

  Synthesis of 15-methylene-eburnamonine from (+)-vincamine, evaluation of anticancer activity, and investigation of mechanism of action by quantitative NMR

  摘要：

  The biological role of installing a critical exocyclic enone into the structure of the alkaloid, (-)-eburnamonine, and characterization of the new chemical reactivity by quantitative NMR without using deuterated solvents are described. This selective modification to a natural product imparts potent anticancer activity as well as bestows chemical reactivity toward nucleophilic thiols, which was measured by quantitative NMR. The synthetic strategy provides an overall conversion of 40%. In the key synthetic step, a modified Peterson olefination was accomplished through the facile release of trifluoroacetate to create the requisite enone in the presence of substantial steric hindrance. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.08.095
• 作为产物：
  描述：

  长春布宁 在 盐酸 、 亚硝酸特丁酯 、 三氟甲磺酸三甲基硅酯 、 potassium tert-butylate 、 三(二甲氨基)锍二氟三甲基硅酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 苯 为溶剂， 反应 5.5h， 生成 (-)-15-methylene-eburnamonine
  参考文献：
  名称：

  Synthesis of 15-methylene-eburnamonine from (+)-vincamine, evaluation of anticancer activity, and investigation of mechanism of action by quantitative NMR

  摘要：

  The biological role of installing a critical exocyclic enone into the structure of the alkaloid, (-)-eburnamonine, and characterization of the new chemical reactivity by quantitative NMR without using deuterated solvents are described. This selective modification to a natural product imparts potent anticancer activity as well as bestows chemical reactivity toward nucleophilic thiols, which was measured by quantitative NMR. The synthetic strategy provides an overall conversion of 40%. In the key synthetic step, a modified Peterson olefination was accomplished through the facile release of trifluoroacetate to create the requisite enone in the presence of substantial steric hindrance. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.08.095

文献信息

• Exploiting the Facile Release of Trifluoroacetate for the α-Methylenation of the Sterically Hindered Carbonyl Groups on (+)-Sclareolide and (−)-Eburnamonine
  作者：Mark V. Riofski、Jinu P. John、Mary M. Zheng、Julia Kirshner、David A. Colby

  DOI：10.1021/jo102114f

  日期：2011.5.20

  applied this method to produce semisynthetic derivatives of the natural products (+)-sclareolide and (−)-eburnamonine, in which the carbonyl group is proximal to bulky functional groups. Mechanistic insight is also provided from a time course of 19F NMR. Biological evaluation of the natural-product-derived enones led to the identification of a derivative of (−)-eburnamonine with significant cytotoxicity

  报道了一种用于羰基的α-甲基化的有效方法，并且该转化通过在烯烃形成过程中容易地消除三氟乙酸盐来完成。该方法代表了在空间障碍情况下对现有方案的改进，并且我们已经证明了该方法在一系列酮，内酰胺和内酯中的实用性。此外，我们已经应用此方法生产了天然产物（+）-香紫苏内酯和（-）-金枪鱼碱的半合成衍生物，其中羰基基团靠近庞大的官能团。还提供19分钟的时间过程的机械洞察力1 H NMR。对天然产物衍生的烯酮的生物学评估导致鉴定出在耐药MDA-MB-231乳腺癌细胞中具有显着细胞毒性（LC 50 = 14.12μM）的（-）-氨丁胺衍生物。
• COMPOSITIONS AND PROCESSES OF PREPARING AND USING THE SAME
  申请人：Colby David A.

  公开号：US20140039182A1

  公开（公告）日：2014-02-06

  The present invention relates to compositions, for example, the DBU/Hexafluoroacetone hydrate salt, and processes of preparing and using the same for the modification of chemical compounds via the release of trifluoroacetate. The DBU/Hexafluoroacetone hydrate salt can perform trifluoromethylation reactions on chemical compounds, such as carbonyl group-containing compounds.

  本发明涉及组合物，例如DBU/六氟丙酮水合物盐，以及制备和使用该组合物通过三氟乙酸的释放来修饰化合物的过程。DBU/六氟丙酮水合物盐可以对化合物进行三氟甲基化反应，例如含羰基的化合物。
• US9359277B2
  申请人：——

  公开号：US9359277B2

  公开（公告）日：2016-06-07
• [EN] COMPOSITIONS AND PROCESSES OF PREPARING AND USING THE SAME<br/>[FR] COMPOSITIONS ET LEURS PROCÉDÉS DE PRÉPARATION ET D'UTILISATION
  申请人：PURDUE RESEARCH FOUNDATION

  公开号：WO2012129384A2

  公开（公告）日：2012-09-27

  The present invention relates to compositions, for example, the DBU/Hexafluoroacetone hydrate salt, and processes of preparing and using the same for the modification of chemical compounds via the release of trifluoroacetate. The DBU/Hexafluoroacetone hydrate salt can perform trifluoromethylation reactions on chemical compounds, such as carbonyl group-containing compounds.
• Synthesis of 15-methylene-eburnamonine from (+)-vincamine, evaluation of anticancer activity, and investigation of mechanism of action by quantitative NMR
  作者：James R. Woods、Mark V. Riofski、Mary M. Zheng、Melissa A. O’Banion、Huaping Mo、Julia Kirshner、David A. Colby

  DOI：10.1016/j.bmcl.2013.08.095

  日期：2013.11

  The biological role of installing a critical exocyclic enone into the structure of the alkaloid, (-)-eburnamonine, and characterization of the new chemical reactivity by quantitative NMR without using deuterated solvents are described. This selective modification to a natural product imparts potent anticancer activity as well as bestows chemical reactivity toward nucleophilic thiols, which was measured by quantitative NMR. The synthetic strategy provides an overall conversion of 40%. In the key synthetic step, a modified Peterson olefination was accomplished through the facile release of trifluoroacetate to create the requisite enone in the presence of substantial steric hindrance. (C) 2013 Elsevier Ltd. All rights reserved.